Visit-to-Visit Blood-Pressure Variability May Predict CV Risk

Marlene Busko

August 06, 2015

BIRMINGHAM, AL — Hypertensive patients with significant changes in blood-pressure readings over several office visits had an increased risk of stroke, MI, heart failure, and death during a 2.8-year follow-up—independent of how well their hypertension was controlled—in a new study[1].

These findings by Dr Paul Muntner (University of Alabama at Birmingham) and colleagues are based on a post hoc analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), which was published July 28, 2015 in the Annals of internal Medicine.

Variability in office blood-pressure readings is not the same as the normal 24-hour or stress-related changes in blood pressure, Muntner explained to heartwire for Medscape. "Both are important, but this [study] is really getting at the variability that is probably due to vascular injury [as opposed to a] response to stressors," he said.

"What we don't have is evidence that lowering blood-pressure variability reduces outcomes," he cautioned. This remains to be determined in further research.

However, variations in visit-to-visit blood-pressure readings can help identify high-risk patients, he noted. "A patient whose blood pressure is generally well controlled [<140/<90 mm Hg] but bouncing around a bit may be at a higher [CV] risk than someone whose blood pressure is consistent." Moreover, these patients do not have extreme fluctuations in systolic blood pressure. "We're not seeing people's blood pressure going from 120 to 160. We're talking about 120 to 135, back to 120, and then to 105," he said.

Invited to comment, Dr Amytis Towfighi (USC Keck School of Medicine, Los Angeles, CA) agreed that "as the evidence mounts regarding the importance of consistency of blood-pressure readings . . . physicians should pay attention to the percentage of time that a patient's blood pressure is under control."

Is Unstable BP an Independent CV Risk Factor?

Until recently, variations in office blood-pressure readings over time were dismissed as random fluctuations, Muntner and colleagues write. However, some newer studies have linked inconsistent clinic blood-pressure readings with a higher risk for stroke and CHD, whereas other studies did not find this association.

To investigate this, the researchers performed a secondary analysis of 25,814 patients from ALLHAT.

From 1994 to 1998, ALLHAT enrolled hypertensive adults aged 55 and older to determine whether initial treatment with a calcium-channel blocker (amlodipine), ACE inhibitor (lisinopril), or alpha-blocker (doxazosin)—each compared with initial treatment with a diuretic (chlorthalidone)—would lower the risk of major CV outcomes.

The patients had blood pressure assessed during 28 months following enrollment, and cardiovascular and mortality outcomes were assessed in 2001 and 2002.

The current analysis excluded patients who received doxazocin (which was no longer recommended in JNC 6 issued in 1997) or had a CVD event or died before the 28-month assessment.

Muntner and colleagues calculated the variability in systolic and diastolic blood pressure for each individual, based on data from follow-up visits at 6, 9, 12, 16, 20, 24, and 28 months after randomization.

The participants were divided into five quintiles of standard deviation in systolic blood pressure: <6.5 mm Hg, 6.5 to <8.7 mm Hg, 8.7 to <11 mm Hg, 11 to <14.4 mm Hg, and >14.4 mm Hg.

From the blood-pressure assessment at 28 months until the study end, 1194 patients had a fatal CHD or nonfatal MI, 1948 patients died, 606 patients had a stroke, and 921 patients had heart failure. Patients with greater variability in visit-to-visit systolic and diastolic blood pressure were more likely to have an adverse outcome.

Risk of Adverse Outcomes, High vs Low Variability in Systolic BPa

Outcome HR (95% CI)b P
Fatal CHD or nonfatal MI 1.30 (1.06–1.59) 0.006
All-cause mortality 1.58 (1.32–1.90) <0.001
Stroke 1.46 (1.06–2.01) 0.013
Heart failure 1.25 (0.97–1.61) 0.084
a. Highest quintile (≥14.4 mm Hg) vs lowest quintile (<6.5 mm Hg) of standard deviations in visit-to-visit readings of systolic blood pressure
b. After adjustment for multiple risk factors including medication adherence and mean systolic blood pressure

"Not Just Noise," but How to Treat Remains Unknown

For patients with wide variations in visit-to-visit blood-pressure readings, clinicians can take a careful patient history to check medication adherence and diet, and they should ensure that blood pressure is being measured in a standard way after the patient has been resting at least 5 minutes, Towfighi said. Patients can take their own blood-pressure readings between office visits and bring in a log that can be reviewed.

Variability in blood-pressure readings is a real phenomenon, Muntner emphasized. "Someone who has variability over one time period tends to have variability over another time period," he said. "It's reproducible. It's not just noise."

In ALLHAT, calcium-channel blockers and diuretics were associated with lower variability, but that doesn't necessarily mean that using these drug classes will lower variability, which will in turn lower cardiovascular disease event rates, Muntner noted. That remains to be determined in further research.

ALLHAT received financial support from the National Heart, Lung, and Blood Institute of the National Institutes of Health and Pfizer; study medications were contributed by Pfizer (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin). Muntner reports grants from the National Institutes of Health during the conduct of the study and grants and personal fees from Amgen outside the submitted work. Disclosures for the coauthors are listed in the article.

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